EARLY EXPERIENCE AND EXPLORATIVE BEHAVIOR IN THE WHITE RAT

Eleven rats were reared in a cage with moving figures. Eleven litter mates were reared in a similar cage but without figures. The rats from the more complex environment showed less locomotor activity in a checkerboard maze and, in a two-lever test box, higher preference for the lever which produced complex visual stimuli. It is proposed that rearing in stimulus poverty increases locomotor activity and reduces curiosity.     

Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats

Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.     

The effect of electric shock on rats' choice between familiar and unfamiliar maze arms: A replication

It is argued that experiments showing that noise and electric shock produce gross changes in rats' locomotor activity are only weak evidence for a relationship between fear and exploration. Stronger evidence comes from an experiment in which fewer shocked than unshocked rats chose the unfamiliar arm of a maze. Certain details of this experiment are unclear, and an attempt is made here to confirm its findings. In one experiment, shocked rats again chose the unfamiliar arm less often than unshocked rats, and in a second experiment it was shown that this finding cannot be explained by saying that shocked rats choose at random. These results are discussed in relation to recent suggestions about exploration in rats.     

Effects of Unilateral Entorhinal Cortex Lesion and Ganglioside GM1 Treatment on Performance in a Novel Water Maze Task

Transient deficits have been reported after unilateral entorhinal cortex (EC) lesion. To determine whether there is a more persistent deficit, adult male Sprague–Dawley rats with electrolytic or sham lesions of the left entorhinal cortex were examined on acquisition of a modified working memory task in the Morris water maze. This delayed matching-to-sample task, with a 1-h intertrial interval, reveals a significant deficit in total distance to platform in both presentation (Trial 1) and matching (Trial 2) in the rats with entorhinal lesions. We have also found that this test can be used to assess significant deficits in perseveration (repeated nonproductive movement) in rats with entorhinal lesions. The deficits can be seen up to 16 days postinjury. Administration of ganglioside GM1 resulted in a moderate improvement in performance in both water maze measures analyzed. All groups (sham operated, lesion with saline treatment, and lesion with ganglioside GM1 treatment) were given three other tests, which were used to evaluate possible contributing factors to deficient water maze performance. A one-trial test for exploration of novel objects revealed no significant, simple working memory deficit in any group. Plus maze testing, to assess possible differences in levels of anxiety or increased activity as a component of water maze performance, also revealed no differences in the three groups. All groups were also similar in motor activity, shown by monitoring of activity levels. The worsened water maze performance observed in rats with EC lesion may be related to deficits in working memory ability within the framework of acquisition of a more complex spatial learning task.     

Wistar rats with high versus low rearing activity differ in radial maze performance

Substantial work has shown that rats although identical in stock, sex, age, and housing conditions can differ considerably in terms of behavior and physiology. Such individual differences, which can be detected by specific behavioral screening tests, are rather stable, that is, they probably reflect a behavioral disposition or trait. Here, we asked whether and how such differences might affect performance in a task of spatial learning and memory, the radial maze. As in our previous work, we used the degree of rearing activity in a novel open field to assign male adult outbred Wistar rats into those with high versus low rearing activity (HRA/LRA rats). They were then tested in a plus-maze for possible differences in anxiety-related behavior. Finally, and most importantly, they were food deprived and underwent maze training using an 8-arm radial maze with four non-baited and four baited arms. One of these arms consistently contained a larger bait size than the other three. In the open field, HRA rats not only showed more rearing behavior, but also more locomotor activity than LRA rats. In the plus-maze, HRA rats again showed more locomotion, but did not differ in open arm time or percentage of open arm entries, that is, conventional measures of anxiety-related behavior. In the radial maze, HRA rats consistently needed less time to consume all pellets than LRA rats, which was due to faster locomotion on the arms and less time spent at the food pits (especially in baited arms) of HRA rats. During the initial days of training, they were also more efficient in obtaining all food pellets available. Furthermore, HRA rats visited more arms and made relatively less reference memory errors than LRA rats. This allowed them to forage food quickly, but was paralleled by more working memory errors than in LRA rats. In general, working memory errors were more frequent in the arm with the large bait size, but there were no indications that HRA and LRA rats responded differently dependent on reward size. Finally, LRA rats lost slightly more weight than HRA rats during the period of food deprivation. These results are discussed with respect to the role of cognitive and motivational mechanisms, which as subject-inherent factors can contribute substantially to inter-individual variability in the radial maze.     

Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor activity of rats: short- and long-term study

The effects of 14-day treatments with nerve growth factor (NGF), basic fibroblast growth factor (b-FGF), or the peptidergic drug Cerebrolysin on postlesion acquisition of a water maze task and on motor activity were evaluated. Rats were tested in the Morris water maze 14 days (early test) and 7 to 8 months (delayed test) after a bilateral lesion of the frontoparietal (sensorimotor) cortex. Only the rats treated with Cerebrolysin performed the water maze task at the level of the nonlesioned controls in the early test. No short-term effect of NGF (6.5 ng/14 days; 38 ng/ml) or b-FGF (17 ng/14 days; 100 ng/ml) treatment was found. The delayed test revealed that water maze performance was restored in rats treated with b-FGF in comparison with intact controls. The data showed that b-FGF can support or initiate processes in the CNS that lead to a delayed functional amelioration and/or compensation for a water maze performance deficit. NGF did not influence the acquisition impairment caused by a sensorimotor cortical lesion. Two-week administration of Cerebrolysin had a time-dependent influence: it attenuated the acquisition deficit and increased the motor activity of rats, both effects declined to the level of lesioned controls within 8 months.     

Effects of ketamine on tunnel maze and water maze performance in the rat

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.     

Individual differences in anxiety trait are related to spatial learning abilities and hippocampal expression of mineralocorticoid receptors

Although high levels of anxiety might be expected to negatively influence learning and memory, it remains to be shown whether individual differences in anxiety may influence spatial learning and memory in outbred rat populations. We have studied this possibility in male Wistar rats whose levels of anxiety were first characterized as either high (HA) or low (LA) according to their behavior in the elevated plus maze or in the open field test. Subsequently, their performance in the Morris water maze was studied, a task dependent on hippocampal activity. Interestingly, LA rats showed a faster acquisition and better memory in the water maze when compared to HA rats. Indeed, this difference in performance could mainly be attributed to the increase in thigmotactic behavior (swimming in circles close to the maze walls) displayed by HA rats during spatial navigation. Glucocorticoids are known to affect the state of anxiety and the hippocampus is the main target of glucocorticoids in the brain. Hence, we investigated whether the hippocampal expression of the two classical corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) differed in the two groups of rats. We found that LA rats displayed higher hippocampal expression of MR but not GR than HA rats. Indeed, the expression levels for these receptors were positively correlated with the amount of time spent by the animals in the open arms of the elevated plus maze. Moreover, we present evidence that the levels of anxiety quantified in the first stages of our study constitute a trait rather than a state. Taken together, this study has generated evidence of a close interaction between the anxiety trait, hippocampal MR expression and the learning abilities of individuals in stressful spatial orientation tasks.     

Anxiolytic effects of repeated victory in male Wistar rats

Recurring evidence suggests that social stress has anxiogenic‐like effects in laboratory rodents. However, despite the fact that competitive situations are stressful, success in competitive situations reduces anxiety in humans. The aim of the present study was to investigate whether repeated experience of winning in aggressive encounters affects anxiety measures in laboratory rodents. Male rats were housed together with a female for 2 weeks. Cohabitation with females was necessary to induce high levels of aggressiveness in these animals. During the second week, half of the male rats were exposed daily for 30 min to an intruder of smaller size, and the other half remained undisturbed in their home cage. Group‐housed male rats were also used as controls. Residents attacked and defeated intruders, who did not retaliate. After the fifth encounter, all animals were tested for anxiety on the elevated plus‐maze. Repeated victory lowered anxiety measures considerably, despite the fact that aggressive encounters are stressful even for the victor. It is concluded that repeated victory has an anxiolytic action in male rats. The similarities with human data suggest that repeated winning in rats can be used as a laboratory model for success‐induced changes in human anxiety. Aggr. Behav. 26:257–261, 2000. © 2000 Wiley‐Liss, Inc.     

An automated device for measuring locomotor activity in rats

An automated plus maze is described that is capable of recording the locomotor activity of 12 rats simultaneously. The system is built around an 8008 microprocessor chip from INTEL. The base of the system is formed by 12 plus mazes in which the activity of the animals under test can be monitored.     

Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment

The effects of aging and of housing in an enriched environment on performance in an 8-arm radial maze were evaluated in young adult (7-8 months) and old (30-33 months) male Brown-Norway rats, using a procedure in which the rats were confined for 8 s to the central platform of the maze between consecutive choices. Although the old rats attained a level of performance which was clearly above change, they were shown to perform worse than the young rats. No performance differences were found between differentially housed rats of the same age group. In a second experiment recovery cycles of visual evoked potentials were determined in the same rats by using paired flashes with an interstimulus time of 400, 300, 200, or 100 ms. Recovery was consistently smaller in the old rats as compared to the young ones. No correlation could be demonstrated, however, between radial maze performance or housing condition and recovery functions of the visual evoked potentials. This finding indicates that a decline in visual sensitivity cannot readily explain the impaired radial maze performance of old rats. Evidence which suggests that age-related hippocampal changes play a major role in the radial maze performance deficit is discussed.     

Rats use a sense of direction to alternate on T-mazes located in adjacent rooms

Lister hooded rats were trained on a forced-sample T-maze alternation task in an environment lacking spatial landmarks. An early study of spontaneous alternation on the T-maze had shown that rats use a "spatial sense" to select alternate maze arms across mazes. As this phenomenon may provide a useful tool for studying the neural substrates of a directional sense, we wished to confirm this finding on a different version of the T-maze task, with well-trained animals. We found that rats successfully selected the appropriate maze arm when the choice phase of the task was presented on a second maze, oriented in the same direction, and located in an adjacent room. However, choice performance fell to chance level when the second maze was oriented 90° relative to the first. This result suggests that the rats do not simply alternate turns across the two environments, but rather that they rely on a sense of direction that is carried across environments. Electronic Publication     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

Effect of exposure to lithium-paired or amphetamine-paired saccharin solution on open arm avoidance in an elevated plus maze

Recent evidence suggests that drug-induced conditioned taste avoidance may be mediated by conditioned fear (e.g., Parker, 2003). The experiments reported here evaluated the effect of exposure to a drug-paired flavor on open arm exploration in an elevated plus maze (EPM), a measure of fear. When rats were tested on a familiar (trial 2) EPM, but not on a novel (trial 1) EPM, prior exposure to a lithium-paired saccharin solution enhanced open arm activity relative to saline-paired saccharin. On the other hand, when rats were exposed to lithium-paired saccharin during plus maze exposure, they displayed suppressed open arm activity relative to unpaired controls when tested in a familiar maze. The pattern of results was specific to the conditional affective properties of the taste, because exposure to unconditional sickness produced by administration of lithium, and unconditionally unpalatable quinine solution did not produce this pattern. These results were interpreted in terms of the opponent process model of motivation; that is, exposure to a lithium-paired flavor elicits conditioned fear which is immediately followed by conditioned relief when the exposure is terminated. On the other hand, exposure to an amphetamine-paired flavor either before or during EPM testing enhanced open arm exploration. Since the strength of taste avoidance did not differ among amphetamine and lithium conditioned rats, these results provide further evidence that the nature of a saccharin-lithium association differs from that of a saccharin-amphetamine association.     

The effects of cache modification on food caching and retrieval behavior by rats

Rats cached pieces of cheese on four different arms of an eight-arm radial maze. On a retrieval test given 45 min later, rats learned to return to arms where food was cached before arms where food had not been cached. Tests were then performed in which cache sites on one side of the maze were always modified (pilfered or degraded), but cache sites on the other side of the maze were left intact. In all of these tests, it was found over repeated trials that rats continued to distribute cached food equally between the two sides of the maze. Measures of the order in which arms were visited showed no caching preference but a preference in food retrieval for the side of the maze where food caches were not altered. These findings suggest that rats’ caching behavior is not affected by its consequences.     

Residential-maze behavior of spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) exhibit elevated levels of ambulation after transfer to a novel environment compared to the Wistar-Kyoto rat (NR). The present experiment compared long-term activity of SHR and NR in a residential maze to determine whether the SHR exhibit elevated levels of locomotor activity under undisturbed, baseline conditions in addition to enhanced reactivity to stimuli. The SHR were much more active visiting more arms of the maze than the NR during the initial hours following transfer to the maze, and during hours around dark onset and light onset. However, the SHR also exhibited higher levels of activity than the NR under baseline conditions. While the NR visited the arm containing food more frequently than other arms, the SHR exhibited no such preference. These data show that both stimulus-induced and basal levels of ambulation are increased in the SHR compared to its normotensive genetical counterpart.     

Extinction-induced "despair" in the water maze, exploratory behavior and fear: effects of chronic antidepressant treatment

In former studies, we found evidence for the hypothesis that withdrawal of negative reinforcement presents a major source for stress and despair. Specifically, the removal of a hidden platform in the water maze induced extinction of previously reinforced escape behavior and behavioral immobility, indicative of "despair", which also correlated with indices of fear. Here, we tested the effects of antidepressants on extinction in the water maze, and expected that such drugs would attenuate the rate of extinction of a conditioned place preference (CPP) and also any emotionally relevant behavior that is induced by the loss of reinforcement, such as immobility. Adult male Wistar rats were trained to escape onto a hidden platform for 10 days. Daily treatment with desipramine hydrochloride (DMI, 10mg/kg) or fluoxetine (FLX, 10 mg/kg) commenced 1 day before the first of 11 extinction trials without the platform, administered 48 h apart, and continued thereafter, as the rats were tested in an open field and elevated-plus maze. As compared to controls, DMI increased the resistance-to-extinction of CPP, attenuated immobility, and increased wall climbing behavior. In the open field, DMI reduced activity levels, but was without effect on traditional fear parameters in the elevated-plus maze. FLX, by contrast, increased immobility during the extinction trials and fear in the elevated-plus maze. The withdrawal of reinforcement induced "despair" that was alleviated by the noradrenaline reuptake inhibitor DMI. The effects of the selective serotonin reuptake inhibitor FLX on immobility and fear may be explained in terms of its side effect profile.     

Effects of pre-exposure to the same or different pattern of extra-maze cues on subsequent extra-maze discrimination

In two experiments, rats learned a spatial discrimination between maze arms defined by their relationship to a variety of extra-maze cues. Prior exposure to the actual arms between which animals were required to discriminate tended to retard subsequent learning (by comparison with a control group either given no pre-exposure to the extra-maze cues or exposed only to arms pointing in the opposite direction), whereas prior exposure to arms intermediate between those used in discrimination training tended to facilitate subsequent learning. These results are consistent with the suggestion that pre-exposure will facilitate discrimination learning when it reduces the associability of features or elements common to the stimuli between which animals are required to discriminate, more than it reduces the associability of the features or elements unique to each.     

Preserved spatial memory in old rats survives 10 months without training

Aged rats with extensive prior training on the radial maze retain the capacity for accurate spatial working memory (WM) for at least 3 months without practice. To investigate the temporal limits of this influence of prior experience we compared the reacquisition of spatial WM by a group of experienced 21.5-month-old rats to the original acquisition by naive 3-month-old rats. The aged rats had received 225 radial maze tests between 3 and 11 months of age. Despite 10 months without practice the old rats rapidly reacquired critical performance. Their reacquisition was markedly superior to original learning by the young rats, even when delays as long as 5 h were imposed between the rats' fourth and fifth choices during the daily tests in the eight-arm maze. Additional tests showed that neither young nor old rats employed a response strategy to maintain accurate spatial WM performance. Experience clearly confers long-lived protection against the otherwise deleterious effects of aging on spatial WM, but the mechanism by which this influence arises is unknown.     

Algorithmic responding on the radial maze in rats does not always imply absence of spatial encoding

Two experiments were conducted to determine whether consistent algorithmic response patterning on 8- and 10-arm versions of the radial maze is independent of spatial encoding. On the 8-arm version well-trained hooded rats were tested in darkness, after maze rotation that rendered room cues ambiguous with respect to arm positions, or with room cues unsystematically relocated. Ambiguous maze rotation was also used with well-trained subjects on the 10-arm version. If algorithmic patterning is a learned, non-spatial strategy, animals using it consistently ought not to have been affected by changes in the spatial layout of the test environment, and the type of pattern used by each subject would have remained constant. On the 8-arm radial maze, responses were most often made to arms 2 or 3 from that just visited. In many animals patterns were interchangeable, switching occurring between preferred angles of turn from day to day. Performance fell when animals were tested in darkness and upon ambiguous maze rotation early (but not later) in training. Testing in darkness increased the angle through which animals turned when responding, perhaps due to the disturbance of intramaze cue use. On the 10-arm maze the “consecutive arm” pattern was used persistently by several animals and appeared to protect their performance from disruption by ambiguous maze rotation. Animals not using rigid patterning were adversely affected. However, on both mazes animals using patterning correctly identified maze arms that had been omitted from otherwise patterned choice sequences. Animals adopted continuous patterning only when spatial encoding had been established. Response patterning appears to serve a mnemonic function and in rats complements rather than replaces the use of a spatial representation of the environment. It was concluded that a complex, flexible relationship exists between spatial functioning and its expression via motor responses.